Process for the preparation of 1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-azetidin-2-one.
This invention relates to a process for preparing 1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-azetidin-2-one, a compound useful as an intermediate in the preparation of hypocholesterolemic agents, and to the preparation of 3(R)-(4-hydroxy-phenyl)-3-methanesulfonyloxy propionic acid methyl ester, a novel intermediate in the above mentioned process.
WO 95/08532 discloses a series of hypocholesterolemic agents comprising 3-hydroxypropyl azetidinones and describes several processes suitable for preparing these azetidinones. WO 93/02048 discloses a process to stereoselectively prepare 3- and 4-substituted azetidinones by cyclization of beta-amino amides. WO 95/08532 and WO 97/45406 disclose a method to prepare 3- and 4-substituted azetidinones by reacting 4-phenylbutyrolactones and 4-methoxybenzylideneaniline. WO97/16424 discloses a method to prepare the desired 3- and 4-substituted azetidinones by reacting 4-fluorocinnamyl bromide and a lactam.
More recently U.S. Pat. No. 6,207,882 describes a process to generate 3- and 4-substituted azetidinones streoselectively using p-fluorobenzoylbutyric acid and chiral 4-phenyloxazolidon-2-ones. U.S. Pat. No. 5,886,171 had also previously described a stereoselective process to the desired azetidinones starting from 3(S)-hydroxy-gamma-lactone. U.S. Pat. No. 6,133,001 describes an enzymatic microbial reduction of a 3-keto azetidinone. Other methods exist in the prior art which teach the process of converting the 3-unsubstituted azetidinone, which is the subject of this patent, into 3-, 4-substituted azetidinone hypocholesterolemic agents, such as by the method described in U.S. Pat. No. 5,856,473.